In this proposed project, we will develop a so-called Dynamic Extremity SPECT (DE-SPECT) system that utilizes the 3-D HEXIETC CZT detector technology and a synthetic compound-eye camera design for dynamic and multi-tracer SPECT imaging of PVD in lower extremities. Peripheral Vascular Disease (PVD) affects approximately 8 million Americans and an estimated 10% of the worldwide population, with increasing prevalence in older individuals. PVD has significant health implications, resulting in progressive limb ischemia that can lead to life-altering claudication, non-healing ulcers, limb amputation, and, in severe cases, death. Despite these numbers and a close association with coronary artery disease, PVD remains a relatively under-diagnosed disease. Diabetic patients often require revascularization along with medical and life style interventions to achieve symptom relief, wound healing and limb salvage and have higher rates of restenosis, and higher mortality rates following revascularization when compared to non- DM patients. Although treating large vessel disease and restoration of skeletal muscle perfusion is important for critical limb ischemia and a critical contributor to intermittent claudication, there are other important metabolic and molecular abnormalities involved that need to be evaluated in conjunction with changes in muscle perfusion in order to optimize therapy. Revascularization of obstructed vessels often results in an incomplete or heterogeneous restoration of flow and does not fully restore the functional limitations in PAD patients with intermittent claudication. The proposed DE-SPECT system could provide a unique non-invasive approach for the comprehensive assessment of molecular and physiological changes of the lower extremities in patients with peripheral vascular disease (PVD) in response to therapeutic interventions and assessing these changes will be critical for optimizing and following PVD therapy.